Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca2+-spikes and cell death in cultured rat hippocampal neurons
Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca 2+ concentration ([Ca 2+ ] i ) sp...
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Published in | The Korean journal of physiology & pharmacology Vol. 26; no. 6; pp. 531 - 540 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
The Korean Physiological Society and The Korean Society of Pharmacology
01.11.2022
|
Subjects | |
Online Access | Get full text |
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Summary: | Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca
2+
concentration ([Ca
2+
]
i
) spikes and neuronal cell death induced by 0.1 mM Mg
2+
and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague–Dawley rats using imaging methods for Ca
2+
and
3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg
2+
concentration ([Mg
2+
]
o
) to 0.1 mM induced repetitive [Ca
2+
]
i
spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl-2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca
2+
]
i
spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca
2+
]
i
spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca
2+
]
i
spikes in the absence or presence of DHPG. The IP
3
receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca
2+
]
i
spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca
2+
]
i
spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca
2+
]
i
spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca
2+
from IP
3
and ryanodine-sensitive intracellular stores and activating TRPC channels. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: S.H.Y. designed this research. J.S.Y. and S.J. conducted experiments. J.S.Y., S.J., andH.J.J. performed data analysis. J.S.Y., S.J., and S.H.Y. wrote the manuscript. |
ISSN: | 1226-4512 2093-3827 |
DOI: | 10.4196/kjpp.2022.26.6.531 |